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PCR Results - Advice appreciated


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#1 August1

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Posted 17 September 2013 - 10:49 AM

Hi everyone,

I was diagnosed with CML in August of 2012. I was put on Gleevac 400 mg. After 7 months on Gleevac my PCR was 5.55%. At 12 months it was at 1.06%. Around that time I started having a lot of GI issues. My oncologist recommended that I try stopping Gleevac therapy for two weeks to see if the symptoms subsided, which they did. I had the GI issues checked out and had a CT scan done, and all came back normal. Following that I switched over to Sprycel. I think I was off the TKIs for just over two weeks. I had another PCR test after being on Sprycel for about two weeks and my PCR was up to 3.7%. So in about one month my PCR rose 2.7%, but for two weeks of that time I had discontinued TKI therapy. I have another PCR test in 6 weeks to follow up on this result.

All other bloodwork is normal including CBC, CMP, and LDH. Of course I am really concerned about the increase in the PCR. Does anyone have experience with stopping therapy and PCR results such as this?

Thanks,

Bill



#2 Trey

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Posted 17 September 2013 - 06:24 PM

That is fairly normal to see a rise in PCR after a couple weeks off drugs, and your increase was not very large.  In fact the Gleevec did not seem to be moving your PCR down very fast anyway, so the switch was a good idea for a couple reasons.  Hopefully the Sprycel will help with both the GI issues and PCR.



#3 August1

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Posted 18 September 2013 - 09:56 AM

Hi Trey,

Thank you, I appreciate the feedback. PCR of 1.062 was the best I'd gotten on Gleevac 400mg since starting treatment about a year ago. The jump in the PCR definitely has me worried, but considering that I had stopped treatment for a couple of weeks, I am hoping this is "normal" and that the readings will improve after switching over to Sprycel. Fingers crossed, this next blood test will be a big one for me.

I am wondering if anyone else out there has had "bumps" in their PCR readings which later stabilized as well?

Thanks again!

Bill



#4 Marnie

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Posted 18 September 2013 - 08:00 PM

Hi, Bill. . .when I was on Gleevec, my PCR plateaued and then rose slightly, which was a concern.  I switched to Sprycel and had an immediate drop in PCR, eventually becoming PCRU.  My last 3 or so tests have remained close to or at PCRU. 

I've been where you are, though my rise in PCR was pretty small.  I'm in a good place now. 

Good luck,

Marnie



#5 August1

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Posted 19 September 2013 - 08:27 AM

Hi Marnie,

Great to hear that you've had a really positive response to Sprycel. That's really wonderful. I am hoping for the same!

I was thinking about it and realized that during my time off of TKIs I also started a new PPI (for acid reflux) called Dexilant. I just did some research and found that it can also impact the absorption of Sprycel so that may have contributed as well.

Although I understand that they typically look a 1 log increase in PCR being indicative of treatment response problem, a 2.7% increase seems like a lot to me for just 30 days. I'm 43 years old with 4 kids so it's hard for me not to be really concerned. I may seek a second opinion to see if mutation analysis or additional cytogenetic screening would be warranted at this point.

Thanks again for your feedback, and best of luck on the Sprycel!

Bill



#6 August1

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Posted 19 September 2013 - 08:47 AM

Trey,

Thanks for your post on the chromosomal analysis (separate thread). That was great information and made for some good nighttime reading. 

So I am trying to understand the "what if" scenarios that could have caused this jump in PCR. It seems like this is always a hot topic for those of us with CML.

My initial BMB did not state any additional mutations, but I'll admit it's hard for me not to be concerned when I see a jump of a full 2.7%. It's less than a 1 log increase, but compared to some of the other posts I see where people get concerned over increases in PCR < .1% it just seems like a lot in such a short time.

In looking at some of the other posts I did find several references to PCR increases after adding other medications or supplements, etc., which may decrease absorption rates of various TKIs. During my time away from TKI therapy I also started a PPI called Dexilant (which apparently impacts with Sprycel absorption) and started taking Calcium, B12, and Magnesium.

So combining the fact that I stopped therapy and added Dexilant and calcium that might explain things a little more.Hmmm. Hindsight is 20/20. I guess I may need to re-evaluate the use of the PPI and calcium?

I guess my next step would be to either wait the six weeks for my next scheduled PCR or get a second opinion and ask for Kinase mutation and cytogenetic testing and another PCR in the interim.

Sorry that I think I'm answering my own question here. Just trying to work this out and appreciate everyone's feedback a ton!

Bill



#7 Trey

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Posted 19 September 2013 - 04:10 PM

Most likely scenario is the Gleevec was just not best for you, and the PCR went up a bit when you stopped taking it.  Happens all the time.  You show no signs of anything else.  The 2.7% increase is within the margin of error for the PCR (1/2 log margin of error -- not very impressive), so don't go by others who worry over smaller increases since they almost always find it was not worth the worry.  The "what if" exercises are not useful without more information. 

You can someday read your grandchildren to sleep from Molecular Cytogenetics Magazine and other such tales of adventure in hunting down and slaying the evil CML dragon.



#8 August1

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Posted 20 September 2013 - 09:51 AM

Trey,

Thanks very much. Your post really helped put my mind at ease and is right in line with what my Oncologist offered as well. I love the analogy on slaying the evil CML dragon! Right now I feel like I've got him by the tail.  

Interestingly, for those out there taking proton pump inhibitors (PPIs) for GERD or acid reflux, I did find quite a bit of information on gastric pH and TKI absorption. In other words, if you eliminate stomach acid you may also decrease uptake of your TKI. This varies from drug to drug as the TKIs all have slightly different delivery mechanisms and it's important to note that there is a difference between uptake in plasma levels and cellular uptake. So it's important to discuss with your Oncologist when appropriate.

The links below apply to dexlansoprazole (Dexilant) and dasatinib (Sprycel) but there is a lot of information out there regarding PPIs and imatinib (Gleevac) as well.

http://www.webmd.com...UG&pagenumber=9

http://www.drugs.com...e-capsules.html

Take care,

Bill



#9 August1

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Posted 13 November 2013 - 04:45 PM

Hi everyone,

Just a quick follow up on my original post. Just got my latest PCR results and it came back at 0.6% IS. So the jump was definitely related to stopping therapy (even for only two weeks) and my response to Sprycel seems to be pretty good. Another follow up in a couple of months.

Take care,

Bill






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